The objective of the proposed study is to develop a histochemical method for the demonstration of cyclic nucleotide phosphodiesterase in the retina. The method is based on lead precipitation of inorganic phosphate liberated from cyclic nucleotides by enzyme action and observation of the electron-opaque lead precipitate with the electron microscope. The histochemical technique will be applied to localize enzyme activity in normal mammalian retina and to evaluate a reported deficiency of phosphodiesterase activity in the photoreceptor cells of mice with hereditary retinal degeneration. Further studies are proposed to evaluate the effect of some pharmacological and natural regulators of phosphodiesterase activity, such as papaverine, catecholamines, and dark adaption. Finally, the histochemical procedure will be applied to the primate retina of rhesus monkeys to evaluate enzyme activity in cones as well as rods.